Samokutyaev served as a Flight Engineer for the International Space Station (ISS) long duration Expedition 27/28 missions.

Hanging in front of the crew, live NASA TV launch footage showed that the dog begun to float as the spacecraft soared skywards, an indication of the weightlessness of space.

[7] After two days of solo flight, the Soyuz TMA-21 spacecraft docked with the International Space Station (ISS) on 6 April at 23:09 UTC.

[8] Samokutyayev concluded his 164-day stay aboard the Space Station, when his spaceship, Soyuz TMA-21 undocked from the Russian segment's Poisk module at 00:38 UTC on 16 September.

[9] On the same day, the Soyuz TMA-21 capsule carrying Samokutyayev, Borisenko and Ron Garan touched down (3:59:39 UTC) at 93 miles southeast of the city of Zhezkazgan in Kazakhstan.

He and cosmonaut Sergey Volkov worked for six hours and 23 minutes performing a variety of tasks for both science and maintenance outside the Russian segment of the ISS.

The cosmonauts removed an antenna that helped guide the Poisk module to a docking in November 2009 and was returned to the ISS at the end of the spacewalk.

BIORISK experiment studies the effect of microbes on spacecraft structures and whether solar activity affects microbial growth.

Finally, Samokutyayev and Volkov took more photographs holding photos of the first cosmonaut Yuri Gagarin, spacecraft designer Sergei Korolyov and Soviet astronautic theory pioneer Konstantin Tsiolkovsky with Earth in the background before entering the Pirs module, closing the hatch and completing the Russian EVA #28.

[citation needed] Samokutyaev and cosmonaut Maksim Surayev performed a spacewalk outside the space station on 22 October 2014.

During the extravehicular activity, Samokutyaev and Surayev dismantled the RK 21-8 Radiometria science payload and the 2ASF1-1 and 2ASF1-2 KURS antennas from the Poisk module.

When the cosmonauts finished operations at the Poisk module, they photographed the surface of the orbital station for specialists to assess its condition later.